Since Project 2 will not provide a sufficient number of cases with severe or prolonged diarrhea in the community, Project 6 will identify host/agent/environmental factors associated with diarrhea in sick, hospitalized children. Under this Project, enteric agents and other host/environmental/organisms factors associated with the need for hospitalization in children with severe diarrhea in our population will be explored. Children ages 0-3 years, who are hospitalized at Soroka Medical Center will provide data for a detailed background/clinical/demographic questionnaire; stools for detailed microbiology assessment; and blood for determination of serological and humoral/cellular immune status. Isolation of specific organisms, e.g. enteroaggregative E. coli, Cryptosporidium, will allow for further in- depth probing as to whether specific strains or other factors in the organism are related to virulence. Controls for hospitalized children will be matched for age and other factors obtained from cases in the community-based study under Project 2. Another major goal os this Project is to examine the effects of two intervention therapies, i.e. treatment with bovine hyperimmune anti- Cryptosporidium colostrum immunoglobulin and a new macrolide antibiotic, azithromycin, on the clinical course of cryptosporidial diarrhea in hospitalized children. These will be performed in a randomized double- blind placebo-controlled study design. Since Cryptosporidium is emerging as an important and frequent organism associated with malnutrition and persistent diarrhea, these intervention studies in children who do not have an underlying primary immune deficiency states have the potential to decrease the morbidity and mortality associated with persistent diarrhea, in many countries.